Established and emerging approaches for the management of dyslipidaemia

Abstract

The key role of dyslipidaemia in determining cardiovascular disease (CVD) has been proved beyond reasonable doubt, and therefore several dietary and pharmacological approaches have been developed. The discovery of statins has provided a very effective approach in reducing cardiovascular risk as documented by the results obtained in clinical trials and in clinical practice. The current efficacy of statins or other drugs, however, comes short of providing the benefit that could derive from a further reduction of LDL cholesterol (LDL-C) in high-risk and very high risk patients. Furthermore, experimental data clearly suggest that other lipoprotein classes beyond LDL play important roles in determining cardiovascular risk. For these reasons a number of new potential drugs are under development in this area. Aim of this review is to discuss the available and the future pharmacological strategies for the management of dyslipidemia.

Figure 1

Emerging targets for dyslipidemia. The novel drugs that are under development for the treatment of dyslipidemia present several mechanisms of action. Emerging therapeutic agents for LDL lowering will: (a) interfere with lipoprotein synthesis in the liver by silencing apolipoprotein B (apoB) expression (1) or inhibiting microsomal triglyceride transfer protein (MTP) activity (2); (b) promote LDL-receptor activity by silencing (3) or blocking (4) proprotein convertase subtilisin/kexin type 9 (PCSK9). Emerging therapeutic agents affecting HDL will: (c) increase HDL-C plasma levels by blocking cholesteryl ester transfer protein (CETP) (5), or inducing apolipoprotein A-I (apoA-I) expression (6), (d) improve HDL activity by mimicking apoA-I (7) or nascent HDL (8) or increase the expression of receptors favoring cholesterol efflux from cells (9). Emerging therapeutic agents for triglycerides lowering will improve the catabolism of triglycerides and the handling fatty acids by peripheral organs (10), by new formulation of omega 3 fatty acids (11) and by inhibiting the expression of apolipoprotein C-III in the liver (12). Specific silencing of apolipoprotein (a) is also under investigation (13).